The 14-3-3 protein is an essential component of cyclic AMP signaling for regulation of chemotaxis and development in Dictyostelium.
The 14-3-3 protein is an essential component of cyclic AMP signaling for regulation of chemotaxis and development in Dictyostelium.
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DOI：
10.1016/j.cellsig.2020.109739
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发表时间：
2020-08
影响因子：
4.8
通讯作者：
Min Li;Chao Quan;Shuai Chen;H. Wang
中科院分区：
文献类型：
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作者：
Min Li;Chao Quan;Shuai Chen;H. Wang
14-3-3蛋白在真核生物中是一种进化上保守的蛋白质，它通过与各种磷酸化靶点结合来调节许多细胞过程。它首先出现在网骨藻中，但其在该生物中的作用知之甚少。在这里，我们表明，下调14-3-3损害趋化性，并导致多尖形成在网骨藻。14-3-3是环腺苷酸（cAMP）信号传导的关键成分，与网骨藻中近百种蛋白质结合，其中包括许多进化上保守的蛋白质。14-3-3 −与其靶点的相互作用响应于发育线索/调节剂（包括饥饿、渗透压应激和cAMP）而上调。cAMP刺激14-3-3 −与鸟嘌呤核苷酸交换因子Gef-Q上的磷酸丝氨酸431结合。有趣的是，Gef-QSer 431 Alamutant而不是野生型Gef-Q蛋白的过表达导致了Dictyosteopathy中的多尖端表型，其部分类似于14-3-3 −缺陷突变体的表型。这些数据表明14-3-3在网柱藻中起着重要的作用，并可能有助于加深我们对真核生物中14-3-3 −相互作用体进化的理解。
The evolutionarily-conserved 14-3-3 proteins regulate many cellular processes through binding to various phosphorylated targets in eukaryotes. It first appears inDictyostelium, however its role in this organism is poorly understood. Here we show that down-regulation of the 14-3-3 impairs chemotaxis and causes multiple-tip formation inDictyostelium. Mechanistically, the 14-3-3 is a critical component of cyclic AMP (cAMP) signaling and binds to nearly a hundred of proteins inDictyostelium, including a number of evolutionarily-conserved proteins. 14-3-3 − interaction with its targets is up-regulated in response to developmental cues/regulators including starvation, osmotic stress and cAMP. cAMP stimulates 14-3-3 − binding to phospho-Ser431 on a guanine nucleotide exchange factor Gef-Q. Interestingly, overexpression of Gef-QSer431Alamutant but not wild-type Gef-Q protein causes a multiple-tip phenotype inDictyostelium, which partially resembles phenotypes of the 14-3-3 − deficient mutant. Collectively, these data demonstrate that the 14-3-3 plays an important role inDictyosteliumand may help to deepen our understanding of the evolution of 14-3-3 − interactomes in eukaryotes.